Programs to promptly diagnose and treat pediatric HIV infection play a critical role in reducing childhood mortality in sub-Saharan Africa. Clinical leaders and policymakers need to understand the long-term benefits and costs of these programs, which may differ in settings with different types of HIV epidemics. South Africa is a middle-income country with a very high HIV prevalence (30%: a generalized HIV epidemic) and excellent access to health services for HIV-infected women and their infants. Cte d'Ivoire is a low-income country with a lower HIV prevalence (3%: a mixed HIV epidemic) and more limited access to HIV-related health services. These two countries represent two of the key types of HIV epidemic in sub-Saharan Africa. The long-term outcomes of pediatric HIV treatment reflect a continuum of events over decades, and thus cannot be fully investigated using traditional methodologies, such as clinical trials or cohort studies. Computer models can add great value to shorter-term clinical studies by projecting survival and healthcare resource utilization over both short and long time horizons; this can assist clinicians and policymakers in prioritizing among many competing demands for limited resources. In addition, computer models can identify factors that will have the greatest influence on survival and costs, and thus outline critical priorities for future research. Through K01 AI078754 and the IMPAACT network, NICHD, NIAID, and NIMH have supported a preliminary model of pediatric HIV disease, the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model. We have assembled an international research team with expertise in pediatric HIV, simulation modeling, and epidemiology, and we have used the CEPAC-Pediatric model to conduct analyses of strategies to prevent pediatric HIV infection that have informed WHO guidelines. We now propose a major expansion of the CEPAC-Pediatric model and the use of our model to evaluate novel strategies to diagnose and treat pediatric HIV in South Africa and Cte d'Ivoire. Our three specific aims are: 1) to determine the most effective and efficient strategies for early infant HIV diagnosis; 2) to investigate the clinical outcomes and cost- effectiveness of HIV treatment initiation strategies for children; and 3) to project the clinical and economic outcomes of strategies for monitoring 1st-line therapy and switching to 2nd-line therapy for HIV-infected children. By reflecting key comparisons between South Africa and Cte d'Ivoire, these analyses will represent many of the clinical and economic conditions that characterize the HIV epidemic in Africa. The project's goals to reduce HIV-related morbidity and mortality align with the mission of NICHD: to ensure that all children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability. The project further meets key goals of the Office of AIDS Research, the PEPFAR Roadmap for Saving Lives, and Millennium Development Goals 6 and 4: to prioritize research for women and vulnerable children, to ensure universal access to HIV treatment for children, and to reduce under-five mortality worldwide.